PD-1、PD-L1在胸腺上皮性肿瘤中表达及其临床意义

Expression and potential clinical roles of PD-1 and PD-L1 in thymic epithelial tumors

目的探讨程序性死亡分子1(PD-1)和程序性死亡配体1(PD-L1)在胸腺上皮性肿瘤(TET_(s))中的表达,与临床病理特征之间的相关性及其意义。方法收集潍坊市人民医院病理科2016—2020年间手术切除TETs标本68例,其中胸腺瘤50例,胸腺癌18例。采用免疫组织化学方法检测所有样本中PD-L1和肿瘤间质浸润性淋巴细胞(TILs)PD-1的表达情况,并分析其与各临床病理特征之间的关系。结果68例TETs中PD-L1阳性率为55.88%(38/68),其中胸腺瘤PD-L1阳性率为48.00%(24/50),胸腺癌PD-L1阳性率为77.78%(14/18),胸腺癌中PD-L1的阳性率显著高于胸腺瘤,差异有统计学意义(P=0.042)。PD-L1表达与性别、年龄、肿瘤大小、有无转移、是否伴有重症肌无力症状和是否放化疗之间的差异均无统计学意义(P>0.05);而与WHO组织学分型、Masaoka分期有关,差异具有统计学意义(P<0.05)。68例TETs中PD-1的阳性率30.88%(21/68),在胸腺瘤中的阳性率为36.00%(18/50),胸腺癌中的阳性率16.67%(3/18),PD-1在胸腺瘤和胸腺癌的阳性率差异无统计学意义(P=0.152);考虑B3型胸腺瘤的生物学行为与胸腺癌类似,将B3型胸腺瘤与胸腺癌合并分析,发现其PD-1的阳性率15.38%(4/26),显著低于其他类型胸腺瘤的阳性率40.48%(17/42),差异有统计学意义(P=0.04);PD-1表达与各临床病理特征之间无相关性(P>0.05);PD-1表达与PD-L1表达之间无相关性(P>0.05)。结论PD-L1表达与TETs的恶性程度明显相关,PD-1表达与组织学分级低相关;阻断PD-L1/PD-1信号通路有望成为TETS免疫治疗的新策略。

Objective To assess the expression levels of programmed death 1(PD-1)and programmed death ligand-1(PD-L1)proteins in thymic epithelial tumors(TETs),and to investigate their relationship with clinicopathological features of the TETs.Methods A total of 68 TET_(s) including 50 thymoma cases and 18 thymic carcinoma cases were collected from 2016 to 2020 in the Department of Pathology,People’s Hospital of Weifang.All cases were diagnosed clearly by pathologists,and the relevant clinical and pathological data were all collected.The expression level of PD-L1 and PD-1 were detected by immunohistochemistry to investigate the expression levels of PD-L1 and PD-1 in TETS and their relationship with clinicopathological features.Results Overall,55.88%samples showed PD-L1 expression(38/68).Of the 50 thymoma samples,48.00%showed PD-L1 expression,and 77.78%(14/18)of thymic cancer samples showed PDL1 expression.Significant difference of the expression level of PD-L1 was found in samples between thymoma and thymic cancer(P=0.042).Meanwhile,the expression level of PD-L1 was also associated with WHO histological typing and Masaoka staging(P<0.05).No significant association was found between the expression level of PD-L1 and sex,age,the size of tumor,tumor metastasis,myasthenia gravis symptoms,radiotherapy and chemotherapy(P>0.05).As for the expression levels of PD-1,30.88%samples showed PD-1 expression(21/68).Of the 50 thymoma samples,36.00%showed PD-1 expression,and 16.67%(3/18)of thymic cancer samples showed PD-1 expression.No significant difference was found on PD-L1 positive expression in samples between thymoma and thymic cancer.The positive rate of PD-1 among B3 thymoma and thymic cancer(4/26,15.38%)was significantly lower than other types of thymoma(17/42,40.48%)when B3 thymoma was enrolled in thymic cancer.No significant association was found between the expression level of PD-1 and clinicopathological features(P>0.05).No significant association was found between the expression level of PD-1 and PD-L1(P>0.05).Conclusion The expression of PD-L1 is correlated with the high degree of malignancy in TETs tissue,while the expression of PD-1 is correlated with the low histological grade.Blocking the PD-L1/PD-1 signaling pathway is expected to be a new strategy for TETS immunotherapy.